Study of the AL3810 in the Treatment of Advanced Solid Tumor

NCT03117101 | Completed Phase 1 DMC

• 1 other identifier: CL1-80881-005
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

This was a monocentric, open label, non-randomised, non-comparative, dose-finding phase I study

Conditions

Advanced Solid Tumors

Keywords

Tolerability Pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Identify Dose-limiting toxicity (DLT)

  To assess the tolerability of AL3810 in patients with advanced solid tumors

  35 days

• Identify maximum tolerated dose (MTD)

  To assess the tolerability of AL3810 in patients with advanced solid tumors

  35 days

Secondary Outcomes (6)

• Cmax (maximum plasma concentration)

  Day0,Day8,Day15,Day22,Day29,Day57

• Tmax (time to maximum plasma concentration)

  Day0,Day8,Day15,Day22,Day29,Day57

• AUC (area under the plasma concentration-time curve)

  Day0,Day8,Day15,Day22,Day29,Day57

• Objective response rate (ORR)

  8 weeks

• progression free survival (PFS)

  8 weeks

Study Arms (1)

Dose escalation/ Dose extension of Lucitanib

EXPERIMENTAL

Dose escalation: Dose Level -1: 5 mg.Dose Level 1:.10 mg.Dose Level 2: 15 mg.Dose Level 3: 20 mg. Dose extension: Once the MTD was reached, the MTD-5 mg dose level was to be extended in order to enrol up to 12 patients (number of patients was to be determined regarding safety data) to better assess the toxicity profile, PK profile and antitumor activity.

Drug: Lucitanib

Interventions

Lucitanib DRUG

Also known as: AL3810

Dose escalation/ Dose extension of Lucitanib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chinese male or female patient aged ≥ 18 years old and ≤ 70 years old.
• Estimated life expectancy ≥ 12 weeks.
• Histologically or cytologically confirmed, locally advanced or metastatic solid tumor, refractory to standard therapy or no standard therapy available.
• Full recovery (to grade ≤ 1) from any prior surgical procedure(s) and from reversible side effects of prior therapy for cancer including radiation therapy, chemotherapy, small molecule therapeutics and immunotherapy.
• Patients should be evaluable according to RECIST criteria, version 1.1.
• Adequate haematological, hepatic and renal functions:
• Absolute neutrophil count (ANC) ≥ 1.5x 10\^9/L Platelet counts ≥ 100 x 10\^9/L. Haemoglobin ≥ 9 g/dL. Creatinine clearance \> 50 mL/min (assessed with MDRD formula). Proteinuria qualitative test \< 1+. If proteinuria qualitative test ≥ 1+, proteinuria over 24 hours should be \< 1.0 g/24hrs.
• INR ≤ 1.5. AST, ALT ≤ 1.5 x Upper Limit of Normal Value (ULN) (≤ 3 x ULN in case of liver metastasis).
• Bilirubin \< 1.5 x ULN.
• Eastern Co-operative Group (ECOG) performance status ≤ 1.
• Ability to swallow oral capsules.
• Negative serum pregnancy test at screening in women of childbearing potential within 7 days prior the study drug intake.
• Willingness and ability to comply with study procedures.
• Signed written Informed Consent Form.

You may not qualify if:

• Foreseeable poor compliance to the study procedures.
• Known active central nervous system (CNS) metastases not controlled by prior surgery or radiotherapy and/or low dose steroids.
• Active second malignancy or history of other malignancy within 2 years, with the exception of non-melanoma skin cancers or carcinoma in situ (CIS) of the breast or cervix or controlled, superficial carcinoma of the bladder.
• Previous treatment with bevacizumab within 3 months before the first day of AL3810 administration.
• Patients who received radiotherapy within 4 weeks of starting study treatment.
• Major surgery within 4 weeks before first day of study drug administration.
• History of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification ≥ 3), angina, myocardial infarction or ventricular arrhythmia.
• Significant cardiovascular disease or condition, including:
• Congestive heart failure requiring therapy. Ventricular and/or supra-ventricular arrhythmia requiring therapy. Severe conduction disturbance (including QTc interval prolongation \> 450 msec \[corrected\], history of severe arrhythmia, or history of familial arrhythmia \[e.g., Wolff-Parkinson-White syndrome\]).
• Angina pectoris requiring therapy. Left ventricular ejection fraction (LVEF) \< 50% evaluated by cardiac ultrasound (ECHO) or Multi Gated Acquisition Scan (MUGA).
• Myocardial infarction (MI) within 6 months prior to administration of the first dose.
• Cardiovascular disease \> Class I, according to the New York Heart Association's (NYHA) Functional Criteria.
• Uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 140mmHg and/or diastolic blood pressure ≥ 90mmHg with optimized antihypertensive therapy or patients treated with ≥2 antihypertensive agents) or systolic blood pressure ≥ 160mmHg and/or diastolic blood pressure ≥ 100mmHg with or without antihypertensive therapy.
• Patients with thromboembolic events \< 12 months prior to treatment start or at high risk of such events.
• Ongoing treatment with warfarin or other oral anticoagulant.

Sponsors & Collaborators

• Haihe Biopharma Co., Ltd.: lead
• Shanghai Institute of Materia Medica, Chinese Academy of Sciences: collaborator

Study Sites (1)

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, 200000, China

Location

MeSH Terms

Interventions

E-3810; Rabeprazole

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Jin Li, M.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

• Junning Cao, M.D.

  Fudan University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 16, 2016
• First Posted: April 17, 2017
• Study Start: March 1, 2014
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: April 17, 2017

Record last verified: 2017-04

Locations

CN (1)